Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: A novel strategy to avoid intraduodenal administration

Venishetty, Vinay Kumar; Chede, Raghavendra; Komuravelli, Rojarani; Adepu, Laxminarayana; Sistla, Ramakrishna; Diwan, Prakash V.

doi:10.1016/j.colsurfb.2012.01.001

Cited by 130 publications

(55 citation statements)

References 20 publications

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“…However, peroral delivery of drug-loaded SLNs is hindered by burst release in gastric media (4). To overcome this drawback, intraduodenal administration (5,6) and protective coating of SLNs have been prescribed (7). The former approach is clinically inadequate for repeated administration drugs, and the latter increases the costs of manufacture because of the additional coating step.…”

Section: Introductionmentioning

confidence: 99%

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

et al. 2016

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Abstract. Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to firstpass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 2 3 factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q 24 ) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.

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Section: Introductionmentioning

confidence: 99%

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

et al. 2016

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“…In addition, it is a substrate of the P-glycoprotein, which is present in the enterocyte membrane [4][5][6]. All these factors together contribute to CARV poor oral bioavailability (20 %) [3,6].…”

Section: Introductionmentioning

confidence: 99%

“…Carvedilol (CARV), chemically known as 1-carbazol-4-yloxy-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol is a non-selective b-blocker that has been extensively used for the treatment of congestive heart failure, hypertension and myocardial infarction [1][2][3]. CARV is a poorly watersoluble active pharmaceutical ingredient (API) and undergoes significant first-pass metabolism [4].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of carvedilol compatibility with lipid excipients for the development of lipid-based drug delivery systems

Silva

Teixeira

Serpa

et al. 2015

J Therm Anal Calorim

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Carvedilol (CARV) is a widely used non-selective b-blocker, which has shown low bioavailability after oral administration (20 %) due to its low water solubility and intense first-pass metabolism. Lipid-based drug delivery systems have been proposed to improve CARV oral bioavailability. An evaluation of drug-excipient compatibility is needed to clarify potential physical and chemical interactions between them and therefore guarantee a correct selection of excipients. However, to date there are no reports on the systematic evaluation of CARV-lipid excipient compatibility. Thus, the aim of this study was to evaluate the compatibility of CARV with the lipid excipients commonly used for the development of lipid-based formulations. Thermal analysis techniques (DTA and TG/DTG), Fourier transform infrared spectroscopy and isothermal stress testing (IST) were used for this purpose. The results of this study showed that 4 of the 10 lipid excipients studied were incompatible with CARV. The strongest thermal and spectroscopic modifications were observed in CARV mixtures with oleic acid, lauric acid, lauroyl polyoxylglycerides (Gelucire Ò 44/14) and glyceryl caprylate/caprate (Capmul Ò MCM). In addition, these mixtures resulted in significant decreases in drug content after aging. On the other hand, palmitic acid, stearic acid, glyceryl behenate (Compritol ATO Ò 188), tribeheninPEG (Emulium Ò 22), polyglyceryl-6-isostearate (Plurol Isostearique Ò ) and diethylene glycol monoethyl ether (Transcutol HP Ò ) were considered good candidates for developing self-emulsifying drug delivery systems and for preparing lipid microparticle or nanoparticle containing CARV. These findings denote the relevance of combining thermal and spectroscopic techniques with thermal stress testing for the accurate determination of druglipid excipient compatibility.

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“…The intermediate step in the production of M-SLNs was based on the addition of SA, which is a lipophilic cationic molecule with a primary amine group, into the lipid matrix, 6 which generates positively charged nanoparticles due to the presence of amino groups on the surface of SLNs. 38 The reaction of unprotected sugars with long-chain fatty amine has been described. 41 In this procedure, the reaction was achieved by ring opening of the unprotected anomeric hydroxyl group of mannose with the amino groups present on the surface of the nanoparticles in acetate buffer (pH 4.0), resulting in the formation of Schiff's base (-N=CH-).…”

Section: Synthesis and Characterization Of M-slnsmentioning

confidence: 99%

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

Vieira¹,

Chaves²,

Pinheiro³

et al. 2016

IJN

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The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box–Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff’s base formation. The variation of the ZP between uncoated (approximately −30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells.

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Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: A novel strategy to avoid intraduodenal administration

Cited by 130 publications

References 20 publications

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Evaluation of carvedilol compatibility with lipid excipients for the development of lipid-based drug delivery systems

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

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